Unfavorably altered fibrin clot properties in patients with active rheumatoid arthritis

Objective

Altered fibrin clot properties have been reported in cardiovascular diseases (CVD) and inflammatory states. Given increased prevalence of CVD in patients with rheumatoid arthritis (RA), we investigated whether fibrin characteristics are also altered in RA patients.

Patients and methods

We studied 46 consecutive RA patients versus 50 controls matched for age and gender. Ex vivo plasma clot permeability, turbidity, tissue-type plasminogen activator (tPA)-induced fibrinolysis, and scanning electron microscopy (SEM) images of clots were evaluated.

Results

Patients with RA had lower clot permeability, faster clot formation, higher maximum clot absorbancy indicating thicker fibrin fibers, maximum clot mass and prolonged fibrinolysis time than controls. Maximum rates of clot lysis were similar in both groups. SEM images showed formation of dense clots with many projections on fibrin fibers. Clot permeability inversely correlated with fibrinogen, tPA, plasminogen activator inhibitor-1 (PAI-1), CRP, platelet count, disease activity score (DAS28) and a marker of oxidative stress, 8-iso-prostaglandin F_2α (r from -0.44 to -0.79; all, p < 0.0001). Similar positive associations were found for clot lysis time (r 0.44 to 0.69; all, p < 0.01). Multiple regression analysis showed that fibrinogen was the only independent predictor of clot permeability (R² = 0.87, p < 0.0001) and lysis time (R² = 0.80, p < 0.003) in RA. Maximum D-dimer levels released from clots, maximum clot turbidity and the time of clot formation were predicted by PAI-1 (all, p < 0.05).

Conclusion

We showed unfavorably altered plasma fibrin clot structure and function in RA, which might contribute to an increased risk of thrombotic events in this disease.